Owing to the diversification of the social life accompanied with the rapid development of the material civilization, there are reported every year an increasing number of patients suffering from vertigo or dizziness. Because the pathogenesis of vertigo is diversified, a variety of drugs, such as vasodilators, antihistaminics, tranquilizers and vitamines are used. These drugs are prescribed to the patient according to his complaint and symptoms. None of these drugs, however, can be a fundamental therapy for vertigo. Recently, new antidinic drugs such as betahistine and diphenidol are used for treatment vertigo or dizziness. Nevertheless, they still have much to be improved in that betahistine is short-acting and that diphenidol has a hallusinogenic action. Thus, anti-vertigo drugs with much higher selectivity to vertigo and longer duration of action should be developed urgently.
From this point of view, the present inventors have searched an anti-vertigo drug acting selectivity on the vestibular function which plays an important role in the cause of vertigo. Spontaneous nystagmus by unilateral destruction of the labyrinth was taken as an index for estimating the anti-vertigo drugs. As a result of a series of studies, it was found that the naphthyridine derivatives represented by the above-shown general formula (I) inhibited markedly the nystagmus and showed much more selectivity, longer duration of action and lower toxicity. These derivatives are also quite novel in chemical structure.
A further study on the pharmacological effect of said compounds revealed a noticeable and selective cerebral vasodilating action. Drugs used at present for the therapy of cerebrovascular disease are mainly vasodilators, including anticoagulants, thrombolytics. Nevertheless, there is no drug that acts selectively on cerebral vasculature and many of these drugs cause postural hypotension. Furthermore, there is no convincing evidence that these drugs are practically useful for patients with cerebrovascular disease. The compounds of the present invention may be of value in improving cerebrovascular disease in view of the fact that they increased markedly the vertebral arterial flow while causing only very weak hypotensive and tachycardiac effects.
The present invention was attained on the basis of these findings.